CN101272818B - Medicament dispenser - Google Patents

Medicament dispenser Download PDF

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Publication number
CN101272818B
CN101272818B CN2006800351868A CN200680035186A CN101272818B CN 101272818 B CN101272818 B CN 101272818B CN 2006800351868 A CN2006800351868 A CN 2006800351868A CN 200680035186 A CN200680035186 A CN 200680035186A CN 101272818 B CN101272818 B CN 101272818B
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Prior art keywords
pill dispenser
lid
ratchet
dispenser according
interface
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CN2006800351868A
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Chinese (zh)
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CN101272818A (en
Inventor
H·A·康奈尔
S·J·哈维
R·W·坦斯利
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Glaxo Group Ltd
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Glaxo Group Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J7/00—Devices for administering medicines orally, e.g. spoons; Pill counting devices; Arrangements for time indication or reminder for taking medicine
    • A61J7/02—Pill counting devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0001—Details of inhalators; Constructional features thereof
    • A61M15/0003—Details of inhalators; Constructional features thereof with means for dispensing more than one drug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0001—Details of inhalators; Constructional features thereof
    • A61M15/0021—Mouthpieces therefor
    • A61M15/0025—Mouthpieces therefor with caps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
    • A61M15/0043—Non-destructive separation of the package, e.g. peeling
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
    • A61M15/0046—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier
    • A61M15/0051—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier the dosages being arranged on a tape, e.g. strips
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
    • A61M15/0053—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type or way of disposal
    • A61M15/0055—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type or way of disposal the used dosages being coiled
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0065—Inhalators with dosage or measuring devices
    • A61M15/0068—Indicating or counting the number of dispensed doses or of remaining doses
    • A61M15/007—Mechanical counters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0065—Inhalators with dosage or measuring devices
    • A61M15/0068—Indicating or counting the number of dispensed doses or of remaining doses
    • A61M15/007—Mechanical counters
    • A61M15/0071—Mechanical counters having a display or indicator
    • A61M15/0075—Mechanical counters having a display or indicator on a disc
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/06—Solids
    • A61M2202/064—Powder

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pulmonology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Anesthesiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Diabetes (AREA)
  • Pain & Pain Management (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Obesity (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Media Introduction/Drainage Providing Device (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
  • Closing Of Containers (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

There is provided a medicament dispenser for use with at least one medicament carrier (100; 300a, 300b) carrying multiple distinct medicament portions. The medicament dispenser comprises a dispensing mechanism (340, 350a, 350b) actuable for dispensing the distinct medicament portions carried by said at least one medicament carrier, a mouthpiece (332), and a cover (330) for said mouthpiece. The cover is movably mounted to the dispenser for sequential movement from a first position, in which said mouthpiece is covered, to a second position, in which said mouthpiece is at least part-uncovered, to a third position in which said mouthpiece is uncovered. The cover is adapted to couple with said dispensing mechanism such that movement of the cover from the second position to the third position, but not the first position to the second position, results in actuation of the dispensing mechanism.

Description

Pill dispenser
Related application
The application requires the priority of No. the 0515584.1st, the UK Patent Application of filing an application on July 28th, 2005, and the full content of this application is attached to herein by reference.
Technical field
The present invention relates to the pill dispenser for minute medicine.The invention particularly relates to the allotter for the medicine of dispense powders or tablet form.
Background of invention
The use of suction apparatus in administration of medication (for example, in the bronchodilatation therapy) is well-known.This device generally includes main body or shell, and pharmaceutical carrier is positioned at this main body or shell.Known suction apparatus comprises that pharmaceutical carrier wherein is those suction apparatus of the bubble-cap band (blister strip) that comprises the powder medicaments of a plurality of discrete doses.This device comprises the mechanism near these dosage usually, usually comprises piercing device or peels off the device of cover plate from substrate sheet.Then can approach and the inhalation of dust medicine.This mechanism also can be used for the medicine of dispense tablets form, wherein peels off cover plate from substrate sheet and manifests tablet in order to remove and be consumed subsequently.
Usually by advancing the band in this device to allow to the opening station to utilize this device near each dosage on continuous basis with the medicine of each discrete doses of making this band continuously and being carried.Known devices comprises by GlaxoSmithKline Plc with trade mark Diskus
Figure 2006800351868_0
The device of selling generally includes the leverage that the user that is connected to band propulsive mechanism (for example, via gear train) is actuated.Therefore, thus user actuate this lever and advance band that the medicine of next discrete doses can be obtained at the opening station.
This device also generally includes interface, and user is air-breathing to realize the inhalation of discrete drug dose by interface.Need to provide protective cover to prevent by dirt or grit pollution to this interface.In use, user removes to manifest this interface with this interface lid before sucking by interface.Some installs, and comprises the Diskus of GlaxoSmithKline Plc
Figure 2006800351868_1
Suction apparatus has the interface lid, and it is attached to and reversibly moves (for example, by the movement that pivots) on the shell of this device and from the position that interface is covered to position that interface is not covered.
Applicant has been recognized from reducing to make device need potentially mobile interface lid to manifest interface and actuation lever to advance band to link up in this device for the angle of required number of steps be ready to.Yet applicant is also recognized such potential problems: user may wish that uncap is used for cleaning etc. to manifest interface, but does not wish that this action also causes the propelling of dosage.In order to address this problem, the applicant has now designed a kind of movably device of interface lid that has, this interface lid can be from first " interface is covered " position movement to middle " interface is not covered " the position, the band propulsive mechanism comes so that this band is pushed in device but then can be moved further to engage.
Brief summary of the invention
According to an aspect of the present invention, provide a kind of pill dispenser, it uses with at least one pharmaceutical carrier that carries multiple different pharmaceutical part, and this pill dispenser comprises:
(a) distributor gear can be actuated this distributor gear to distribute the different pharmaceutical part by this at least one pharmaceutical carrier was carried;
(b) interface; And
(c) be used for the lid of this interface, this lid is installed to the primary importance not to be covered from this interface on this allotter movably, is interfaced to the second position that small part is not covered to this, the 3rd position continuous moving that is not covered to this interface;
Wherein this lid is suitable for connecting this distributor gear so that this lid moves from the second position to the 3rd position movement rather than from primary importance to the second position and causes actuating of this distributor gear.
According to a further aspect in the invention, provide a kind of pill dispenser, its pharmaceutical carrier with one or more elongated form uses, and each pharmaceutical carrier has its multiple different drug dose that carries, and this pill dispenser comprises:
(a) shell;
(b) distributor gear in this shell, it is used for distributing each different pharmaceutical dosage part of carrying of these one or more pharmaceutical carriers, and this distributor gear comprises:
I) receiving station, it is used for receiving these one or more pharmaceutical carriers each;
Ii) releasing device, it is used for when receiving pharmaceutical carrier by this receiving station from these one or more pharmaceutical carriers each discharging different pharmaceutical dosage part;
Iii) outlet, its with partly be communicated with by each this different pharmaceutical dosage in releasable these the one or more pharmaceutical carriers of this releasing device; And
Iv) indexer (indexer), it is used for each different pharmaceutical dosage part of these one or more pharmaceutical carriers of calibration (index) individually;
(c) be located at interface on the shell, it can be communicated with this outlet; And
(d) lid that is used for this interface that is connected movably with shell, the primary importance that this lid can be covered from this interface is interfaced to the second position that small part is not covered to this and moves,
Wherein, this lid can connect this distributor gear so that this lid causes actuating of this distributor gear from being moved further of the second position to the three positions.
What pill dispenser of the present invention was preferably handed can manual allotter.
Pill dispenser of the present invention is inhaler preferably, in particular Diskus (DPI).Generally speaking, DPI breathes actuation type; That is, the patient interface air-breathing cause/pass the inspiratory airflow of DPI, this inspiratory airflow is carried drug powder secretly in patient's respiratory tract from pharmaceutical carrier.
In the first embodiment of the present invention, pill dispenser is designed to receive the pharmaceutical carrier of single (alternatively) elongated form.
In the second embodiment of the present invention, pill dispenser is designed to receive the pharmaceutical carrier of a plurality of (alternatively) elongated form.Preferably, pill dispenser is designed to receive two to four this pharmaceutical carriers, more preferably two such carriers.Suitably, under the situation of this second embodiment, the different pharmaceutical dosage of each release that can be from a plurality of pharmaceutical carriers part comprises the combination product of limiting dose in combination.That is to say that when combining (for example, when discharging), different active medicine dosage partly forms " how active " Drug therapy of single dose.
The suitable pharmaceutical carrier that is used for pill dispenser of the present invention has a plurality of various dose parts that it carries.The various dose part is arranged in isolated mode on carrier usually, and more preferably progressive arrangement (for example, sequence is progressive) is so that can be individually near each dosage part.
The term pharmaceutical carrier is used for defining the carrier of any appropriate format in this article.Suitably, the pharmaceutical carrier of each elongated form is the form of band or belt.One preferred aspect, carrier has the form of blister package, but it also can (for example) comprises by any special process (comprise printing, smear and the vacuum occlusion) carrier of coated medicament in the above.
In one aspect, pharmaceutical carrier comprises the blister package of laminate form.Suitably, laminate comprises the material that selects in the group that forms to metal forming, organic polymer materials and paper.Suitably metal forming comprises aluminium foil or tinfoil paper, and its thickness is 5 to 100 μ m, and 10 to 50 μ m preferably are such as 20 to 30 μ m.Suitably organic polymer materials comprises polyethylene, polypropylene, polrvinyl chloride and polyethylene terephthalate.
Suitably approach drug dose part in the capsule that is included in elongate strip band forms carrier near device by any, comprise and tear, pierce through or capsule that strip off is relevant.
A kind of suitable blister package form pharmaceutical carrier comprises strippable bubble-cap band.Suitably, this strippable bubble-cap band comprises substrate sheet and cover plate, form bubble-cap and be used for comprising different drug dose parts to limit capsule within it in substrate sheet, except the bubble-cap zone, this cover plate is sealed on the substrate sheet airtightly so that cover plate and substrate sheet can be stripped.The usually each other sealing on their the whole width except forward end of substrate sheet and cover plate is in their usually fully each other sealings of forward end.Therefore, provide substrate sheet forward end and cover plate forward end separately in the end of band.Respective substrates sheet and cover plate strippingly be separated from each other with (for example, individually) to discharge the inclusions in each capsule.
Suitably, cover plate comprises following at least continuous layer: (a) paper; It adhesively is attached to (b) polyester; Polyester adhesively is attached to (c) aluminum paper tinsel; Aluminium foil scribbles the heat-sealing lacquer and is used for being attached to substrate sheet.Can select every layer thickness according to desired character but be typically about 5 to 200 microns, 10 to 50 microns especially.
Suitably, substrate sheet comprises following at least continuous layer: (a) orientation polyamide (OPA); It adhesively is attached to (b) aluminum paper tinsel; Aluminium foil adhesively is attached to (c) and comprises the 3rd layer of polymeric material (for example, polrvinyl chloride).
Can adopt various known technology that cover plate and substrate sheet are bonded together and then seal the bubble-cap of peelable bubble-cap band.This method comprises adhesive bond, thermometal combination, thermometal welding, radio-frequency welding, laser weld, ultra-sonic welded and hot rolled circular steel sealing.The cover plate of peelable bubble-cap band and substrate sheet can seal by " cold forming " encapsulating method especially, and it can carry out in the temperature that is lower than conventional heat seal method.Medicine or pharmaceutical formulation that this " cold forming " encapsulating method is specially adapted in being contained in bubble-cap are the situations of temperature-sensitive (for example, degradation or degeneration when heating).Suitably at 150 to 250 ℃, more preferably carry out by 210 to 240 ℃ temperature in scope for " cold forming " encapsulating method.
A particular aspects, the pharmaceutical carrier that the first elongated form pharmaceutical carrier has its a plurality of different single active medicine dosage that carries and the second elongated form has its a plurality of different many activity of carrying (especially, double activated dosage part, that is, comprise two kinds of active component) the drug dose part.This list active pharmaceutical ingredient and these many active pharmaceutical ingredients comprise the composition of medicine product of restriction in combination.
Suitably, provide a plurality of different dosage with uniform sequence to each pharmaceutical carrier.Especially, the interval (that is, spacing) between each dosage part is uniform in whole sequence.Yet on the other hand, interval (that is, spacing) may be (that is, non-homogeneous) that changes on whole sequence.In concrete example, spacing can reduce gradually on whole sequence or little by little increase.
In the situation of the pharmaceutical carrier that a plurality of elongated form are provided to pill dispenser, they may be arranged with any suitable configuration.A preferred configuration is " side by side " configuration, and wherein (for example) two carriers (for example, the bubble-cap band of two coilings) are arranged in the allotter and place in side direction aligned with each otherly.Another preferred disposition is " double-decker " (" double decker ") configuration, wherein (for example) two carriers (for example, the bubble-cap band of two coilings share same coiling axis) are arranged in the allotter top at another and place.
This shell can take any suitable shape or form in order to hold other part of pill dispenser.A particular aspects, this shell takes to comprise the form of the housing of two and half shells, and this two and half shell joint is combined and forms the on the whole shell of hull shape.
Suitably, be suitable for holding in the situation of a plurality of pharmaceutical carriers at pill dispenser, some of this distributor gear or all members are common in these pharmaceutical carriers each.Advantage with common member is to reduce the number of the separate part in the pill dispenser.
In other side, can be suitable for connecting in some aspects the action of noncomitant those members.Realize connecting by any appropriate ways, comprise mechanical linkage (for example, altogether gear drive or via applicable link arm/coupling bar) or control dynamo-electric the connection.The advantage that connects is that the mode that can connect realizes the calibration of each pharmaceutical carrier/propelling.
In other side, distributor gear most of or even all members be different.A particular aspects, thereby allotter is set so that each in one or more pharmaceutical carrier can be provided by calibration/propelling independently the chance of complicated dose mode, wherein can near any combination of a plurality of bands or in fact any.
Also be susceptible to wherein exist the embodiment of the single receiving station that can receive a plurality of pharmaceutical carriers and wherein each pharmaceutical carrier by the embodiment of different (that is, individual other) receiving station's reception.In the latter case, can connect or not connect other receiving station.
This releasing device can have any appropriate format.Be in the situation of blister strips band forms at elongated pharmaceutical carrier, this releasing device can (for example) comprise for destroying, pierce through, tear or taking other method near the device of this bubble-cap.One certain preferred aspect, be in the situation of strippable blister strips band forms at pharmaceutical carrier, this releasing device comprises the device for strip off bubble-cap band.In one aspect of the invention, near each the bubble-cap band strip off tip of the restriction of allotter or dovetail part.
This outlet can have any suitable form, but takes especially to be directed to for the drug dose that will discharge the form of the manifold of interface.
Used term " interface " is used in reference to a kind of element in this article, and the patient can be air-breathing by this element.In one aspect, the patient interface is placed he the mouth situation under carry out this suction by oral-cavity device.Aspect alternative, interface comprises that nozzle is used to be inserted into patient's nasal cavity.
Preferably single outlet of outlet, when drug moiety was discharged by this releasing device, single outlet was communicated with from one or more different drug moieties.For example, be communicated with via common air guiding device (for example, forming air hose or manifold), this air guiding device is communicated with interface.So the patient can pass the interface inspiration and this breathing is delivered to the drug moiety that discharges by common air guiding device, thereby can the Sucked medicine product.
The calibration of indexer occurs usually in a continuous manner, for example, approaches the part that becomes sequence to arrange continuously along the length of elongate carrier.Exist in the situation of a plurality of pharmaceutical carriers, the calibration of each carrier can be arranged to occur in paired mode, that is to say that each is by the while calibration.
Aspect preferred, pharmaceutical carrier comprises strippable bubble-cap band.Aspect this, releasing device comprises that suitably substrate sheet and cover plate that detacher is used for each strippable band of strip off open capsule.Suitably, detacher comprises that covering driver (lid driver) is used for pulling open cover plate from the substrate sheet of the capsule that receives at the opening station.
Preferably, the invention provides a kind of pill dispenser, it is used for the pharmaceutical carrier of one or more blister strips band forms, each pharmaceutical carrier has a plurality of different capsules and is used for comprising the drug dose part, wherein these capsules are spaced apart and be defined between them along two peelable length fixed to one another, and wherein this distributor gear comprises:
A) opening station, it is used for receiving the capsule of these one or more pharmaceutical carriers;
B) detacher, it is positioned to be bonded on the substrate sheet of the capsule that receives in this opening station and cover plate so that this substrate sheet and this cover plate strip off are opened this capsule;
C) outlet, it is positioned to be communicated with the capsule of opening, user can be by this outlet from this capsule of opening near the drug dose part; And
D) indexer, it is used for the individually different capsule of these one or more pharmaceutical carriers of calibration.
Suitably, holding in the situation of a plurality of elongated pharmaceutical carriers, providing common opening station to be used for receiving each capsule of a plurality of pharmaceutical carriers.On the other hand, provide different opening stations to be used for receiving the capsule of each pharmaceutical carrier.Suitably, different opening stations utilizes communicating passage or other device and links to allow the independent medicine that discharges to gather together.
Suitably, detacher (that is, stripping off device) acts on the pharmaceutical carrier of these one or more peelable strips.Detacher is bonded on substrate sheet and the cover plate of the capsule that the opening station receives and opens capsule with strip off substrate sheet and cover plate.In one aspect, common detacher acts on the pharmaceutical carrier of each peelable strips.On the other hand, each peelable band acts on each peelable band by its (that is, independent) detacher of controlling oneself.
Suitably, detacher comprises and covers cover plate and the substrate sheet that driver is used for pulling open the capsule that receives at the opening station.
In one aspect, the lid driver comprises wheel, and cover plate is wrapped on this wheel, and the lid wheel has effective twisting surface, and when the tension force in the cover plate increased, this effective twisting surface kept approximately constant.In one aspect, this realizes by covering driver and being finish-machined to " contractile wheel ", wherein along with becoming, cover plate is wound on it, wheel shrinks (that is, the diameter of wheel self reduces) effective coiling diameter (being limited by wheel and the diameter that is wound into the band on the wheel) to give the total approximately constant of wheel.Suitably, should " contractile wheel " comprise a plurality of resilient flexible arms, each arm is therefrom with respect to the angled extension of radius.Looper is initially to be fixed to cover plate on the wheel in these resilient flexible arms one of the front end of cover plate.
Perhaps, the lid driver comprises wheel, and cover plate is wound into and covers on the wheel, and this cover plate wheel has effective twisting surface, and along with cover plate is wound on the wheel, effectively the effective diameter of twisting surface increases behind each use allotter.Then the device that affords redress compensates this increase, otherwise this increase will cause the variation of the tension force that cover plate experiences on its length and therefore it calibration over time.
In one aspect, allotter comprises compensation arrangement, and this compensation arrangement is being used for reducing any increase that the length of this cover plate between them compensates the diameter of effective twisting surface of cover plate wheel during the use allotter between this opening station and this cover plate wheel.
In one aspect, this compensation arrangement is taked the form at the torsion spring of lid driver installation, and it affords redress torsion so that the tension force that provides at cover plate keeps approximately constant in the length of bubble-cap band to the lid driver.
Suitably, this allotter comprises guiding piece, and it is used at the opening station along independent Route guiding cover plate and substrate sheet.Around this leader cover plate is delivered to and covers on the driver.In one aspect, this guiding piece comprises cylinder mechanism.Cover on the driver on the cylinder cover plate being fed to.
Suitably, indexer comprises rotatable divided wheel, have recess in this divided wheel, this divided wheel can engage so that these recesses respectively receive the corresponding capsule of the substrate sheet of the bubble-cap band that uses with this pill dispenser with the pharmaceutical carrier that is used for this pill dispenser.
Suitably, the shell of this pill dispenser comprises the first chamber and the second chamber in addition, be provided with at first at least one pharmaceutical carrier and distribute this pharmaceutical carrier from this first chamber in this first chamber, this second chamber is used for receiving the part of using of substrate sheet after substrate sheet is separated around the divided wheel calibration and with cover plate.Suitably, this first chamber separates by wall with this second chamber.In one aspect, this wall is movably to adjust the size of this first chamber and this second chamber.On the other hand, this wall is installed pivotly.Perhaps, this wall is installed slidably.
Suitably, by suitable installation (such as, pivot to install) lid is installed on the shell.
Lid is reversible and allows reversibly to cover and at least part of this interface that do not cover to the movement of its second position from its primary importance.In addition, this reversible moving from the primary importance to the second position does not cause any of distributor gear to actuate.
During from the second position to the 3rd position movement, lid connects (for example, engaging directly or indirectly) this distributor gear in order to cause actuating of it at lid.
Preferably, lid movement to the 3rd position from the primary importance to the second position is along the movement that limits the path.This path can (for example) be linear or arc (for example around rotation axis).
Suitably, the character in this path and direction are limited by the installation form that lid is installed on the shell.In one aspect, limiting in the enclosure track be used for to receive the track follower (track follower) be located on the lid and limits suitable path in the process along this track.
Perhaps, lid is arranged to be rotated movement around axis.Suitably, lid and ratchet interact, and ratchet and travelling gear interact to drive distributor gear.Suitably, in primary importance, ratchet and travelling gear are spaced apart and in the second position, ratchet engages with travelling gear so that its be moved further (for example, to the 3rd position) causes the movement of travelling gear and the therefore propelling of distributor gear.
Suitably, ratchet and/or travelling gear are provided with the anti-part that returns and return (that is, reversible) rotation with what prevent it.
Alternatively, pill dispenser of the present invention comprises and actuating or number of times that dose counter is used for number of times that the counting indexer actuates or discharges from the dosage of pill dispenser.The number of the number of the dosage to be used that this dose counter count enable is remaining or the dosage that has used.Dose counter can be mechanical type or electronic form.
Alternatively, pill dispenser also comprises electronic data management system, and this electronic data management system has input/output capabilities and comprises for storage data storage device; Be used for the microprocessor to this data executable operations; And be used for emission and these data or with the signal relevant to the result of the operation of data.Electronic data management system can form with the main body of this allotter is whole.Perhaps, this electronic data management system forms the part of the elementary cell that can reversibly be associated with this main body.
According to a further aspect in the invention, provide allotter of the present invention to be used for distributing the purposes of drug products.
By detailed description hereinafter and the appended claims of example embodiment, other side of the present invention and feature will become apparent.
The accompanying drawing summary
Now introduce the present invention referring to accompanying drawing, in the accompanying drawings:
Fig. 1 shows the perspective view that is suitable in conjunction with the pharmaceutical carrier of pill dispenser use of the present invention;
Fig. 2 a to Fig. 2 e show make the first pill dispenser of the present invention be ready to for the perspective view of consecutive steps;
Fig. 3 a to Fig. 3 c show make the second pill dispenser of the present invention be ready to for the perspective view of consecutive steps;
Fig. 4 a to Fig. 4 c show make the second pill dispenser be ready to for the side view of consecutive steps, wherein, do not having that this allotter is shown in the situation of dispenser housing;
Fig. 5 shows the decomposition diagram of the gear mechanism of the second pill dispenser;
Fig. 6 a to Fig. 6 c with the consecutive steps corresponding with the consecutive steps of Fig. 3 a to Fig. 3 c and Fig. 4 a to Fig. 4 c show be ready to for the time the gear mechanism side view detail;
Fig. 7 shows the ratchet of the second pill dispenser and " prevents returning " side view of the details of mechanism;
Fig. 8 shows the distributor gear of the second pill dispenser and the side view of pharmaceutical carrier;
Fig. 9 shows the decomposed figure of the second pill dispenser that does not have the pill dispenser interface;
Figure 10 shows the cutaway view of the second pill dispenser;
Figure 11 shows the interface of the second pill dispenser and the cutaway view of manifold component;
Figure 12 shows the plane graph for the first manifold of interface and manifold component; And
Figure 13 shows the plane graph for the second manifold of interface and manifold component.
Accompanying drawing describes in detail
Fig. 1 shows the pharmaceutical carrier 100 that is suitable in conjunction with the present invention's use, and this carrier 100 is DISKUS of GlaxoSmithKline
Figure 2006800351868_2
ADVAIR
Figure 2006800351868_3
Used type in the inhaler.
Pharmaceutical carrier comprises and defines a plurality of capsules 104,106,108 flexible strip 102, and each in these capsules comprises the form that is suitable for sucking and with the part of the drug dose of the form of powder.According to the present invention, usually in single pill dispenser, adopt a plurality of such bands 102, wherein each band provides the composition drug dose of composition of medicine product.Each band can have identical size and/or comprise identical dose value (for example, volume or quality), perhaps in alternative, adopts the band that has different sizes and/or comprise the various dose value capable of being combinedly.
Band comprises substrate sheet 110 and cover plate 112, forms bubble-cap limiting capsule 104,106,108 in substrate sheet 110, except bubble-cap zone outer cover sheet 112 is sealed on the substrate sheet airtightly so that cover plate 112 and substrate sheet 110 can be stripped.Except leading section 114,116, sheet 110,112 is each other sealing on their whole width, and at leading section 114,116, they are fully not each other sealing preferably.
Each is formed cover plate 112 and substrate sheet 110 by the plastic/aluminium laminate and suitably passes through heat seal and adhering to each other.Cover plate 112 comprises at least one following continuous layer: (a) paper; It adhesively is attached to (b) polyester; Polyester adhesively is attached to (c) aluminum paper tinsel; Aluminium foil scribbles the heat-sealing lacquer and is attached to substrate sheet.Substrate sheet 100 comprises following at least continuous layer: (a) orientation polyamide (OPA); It adhesively is attached to (b) aluminum paper tinsel; Aluminium foil adhesively is attached to (c) and comprises the 3rd layer of polymeric material (for example, polrvinyl chloride).
Band 102 is shown to have an elongated capsule 104,106,108, its with respect to the length of band 102 at extending transversely.This suits because this so that a large amount of capsule 104,106,108 can provide with continuous arrangement along given band 102 length.Band 102 can (for example) be provided with 60 or 100 capsules, but should be appreciated that band 102 can have the capsule of any proper number.
In the preferred embodiment (hereinafter referring to Fig. 2 to Figure 13 introduction) of the first pill dispenser according to the present invention and the second pill dispenser, allotter comprises same flexible strip 102, the capsule 104,106,108 of these bands be of similar shape and the size and along the band length equidistant apart.Comprise identical drug powder in the capsule of each band, the content in other capsule of content in each capsule of band (dosage part) and this band is identical.Yet a band can have at least a active component that is different from another band in its drug powder.Therefore, in use, the patient can suck a dosage part from each band simultaneously, and the dosage of combination partly consists of how active fixed dosage therapy.
Fig. 2 a to Fig. 2 e show be used to make of the present invention hand-held can manual pill dispenser prepare for consecutive steps, the allotter in this specific embodiment is Diskus (DPI).For for simplicity, in each accompanying drawing just labelling the parts of in corresponding introduction, mentioning.
Fig. 2 a shows the pill dispenser that comprises shell 220, limits track 222 and be used for receiving the follower (can not see) of being located on the interface lid 230 in shell 220.In use, interface lid 230 path movement that can limit along the relation between follower and the track 222.In Fig. 2 a, interface lid 230 can't see the primary importance of interface.In other words, lid 230 has covered and has protected interface.Also being provided with window 224 on shell 220, can seeing dose counting labelling 225 by this window 224, is " 30 " in this situation.
In Fig. 2 b, interface lid 230 has moved to the second position that interface 232 is not covered.What can also see now is lock 226 the part that is clasped, its with interface lid 230 on like parts (can not see) interaction when being in the primary importance of Fig. 2 a, lid 230 is locked in the appropriate location.The yet activator batching counter (unshowned mechanism) not of distributor gear (not shown) in the allotter is not actuated in the movement of lid 230 from the primary importance to the second position.
In Fig. 2 c, interface lid 230 further moves to the 3rd position along track 222, and in the 3rd position, the part of lid 230 extends beyond the base 221 of shell.Owing to from being moved further of the second position to the three positions, having actuated the distributor gear in the allotter (can not see) and be used for sucking in order to can obtain drug dose.In other words, now, pill dispenser be ready to for.This moves actuating in order to reduce 225 1 units of dose counting labelling of the dose counter that also caused pill dispenser, has become new reading " 29 " here.
In Fig. 2 d, pill dispenser is provided for the patient to suck by interface 232.
After using, interface lid 230 turns back to primary importance (that is, shown in Fig. 2 a).This storage corresponding to allotter (" interface is protected ") position.
Therefore, visible the first pill dispenser provides the movement of interface lid 230 to actuate also (in this embodiment) also activator batching counter of allotter.The first pill dispenser also provides lid 230 not actuate also (in this embodiment) activator batching counter not of allotter to the movement that partially opens position (primary importance).This allows the patient to clean interface 232 and reduces the careless or unexpected probability of using of allotter, when interface lid 230 is moved back and forth or played with to (for example) the patient.
Fig. 3 a to Fig. 3 c and Fig. 4 a to Fig. 4 c respectively show make the of the present invention second hand-held available manual pill dispenser be ready to for corresponding consecutive steps, allotter is DPI equally in this specific embodiment.For for simplicity, in each accompanying drawing just labelling the parts of in corresponding introduction, mentioning.
The second pill dispenser is disclosed type in US-A-2005/0154491 (people such as Anderson), and the full content of this application is combined in herein by reference.That is to say that the second pill dispenser is provided with two pharmaceutical carriers (bubble-cap band) (referring to Fig. 8, label 300a, 300b) as shown in Figure 1.Comprise identical drug powder in each in its capsule of first band in these bands, and the content of active component is also identical in each capsule of this band.Other band comprises common drug powder in each in its capsule equally, comprises equally identical active component content in each capsule.Drug powder in each band can comprise the mixture of single-activity composition or active component.Yet the drug powder in a band can be included at least a active component that does not contain in the alternative in vitro test.As being described in further detail hereinafter, when operation the second pill dispenser, the capsule of each bubble-cap band is stripped to expose the different pharmaceutical powder in it.Then, the patient is upper air-breathing to suck simultaneously the powder in the capsule of opening at band 300a, 300b at interface (Fig. 3 c, label 332).Therefore the patient receives the drug powder of the dosage of fixing metering, the corresponding dosage part of the different pharmaceutical powder constituent in each capsule.
Fig. 3 a and Fig. 4 a show the pill dispenser that comprises the shell 320 that is provided with interface lid 330.As from Fig. 4 a as seen, interface lid 330 has arm 334, and it is provided with for the installation aperture 336 of installing, and interacts in order to the ratchet 346 with complicated gear mechanism 340.In use, interface lid 330 is rotatably mobile around the axis that the rotation axis of ratchet 346 limits.In Fig. 3 a and Fig. 4 a, interface lid 330 is in the primary importance that interface is covered by it.Shell 320 also is provided with window 324, can see the dose counting labelling 325 of dose counter (not shown) by this window 324.
In Fig. 3 b and Fig. 4 b, interface lid 330 has rotated to the second position that interface lid 332 parts are not covered, but be not actuated at this position gear mechanism 340 and the distributor gear that is associated (as more specifically introducing hereinafter), therefore do not provide drug dose to be used for sucking.In addition, actuating of propellant batching counter (not shown) not, so count tag remains unchanged.
In Fig. 3 c and Fig. 4 c, interface lid 330 has been further rotated the 3rd position not cover or to open interface 332 fully.In this position, the part of lid 330 almost extends to the base 321 of shell 320.Owing to from being moved further of the second position to the three positions, having actuated the gear mechanism in the allotter (more specifically introducing referring to Fig. 5 and Fig. 6 a hereinafter) and distributor gear (more specifically introducing referring to Fig. 8 hereinafter) and therefore made drug dose can be used for sucking.In other words, pill dispenser be ready to now for.This moves the actuating in order to reduce 325 1 units of dose counting labelling of dose counter (mechanism can not see) that has also caused pill dispenser and becomes new reading " 29 ".
After using, interface lid 330 turns back to primary importance (that is, shown in Fig. 3 a and Fig. 4 a).This storage corresponding to allotter (" interface is protected ") position.
Now referring to Fig. 5, can see that shell 320 is provided with interface 332, this interface 332 interacts with manifold 450, and manifold 450 is configured in use to suck for the patient from the capsule guide drugs powder of opening at each pharmaceutical carrier 300a, the 300b of opening station 327 (referring to Fig. 8).
Fig. 5 also shows the aspect of the gear mechanism 340 of the second pill dispenser of the present invention.Can see that shell 320 is provided with the parts that inner chassis 328 is used for outwards receiving gear mechanism 340.In this chassis 328 and referring to Fig. 8, find out better, provide mirror image (left and right) distributor gear 350a, 350b to be used for a minute medicine.Can think that gear mechanism 340 forms the part of distributor gear 350a, 350b.
More specifically referring to Fig. 8, the bubble-cap band 300b that the first bubble-cap band 300a and second that contains medicine contains medicine is positioned in the 303a of left chamber and right chamber 303b on chassis 328.Each bubble-cap band 300a, 300b are engaged among corresponding many capsules divided wheel 360a, the 360b, and divided wheel 360a, 360b are the DISKUS at GlaxoSmithKline
Figure 2006800351868_4
Inhaler (as in US-A-2005/0126568 people such as () Davies referring to Figure 16 introduction and the divided wheel 416 of showing) in and in " two band " suction apparatus of US-A-2005/0154491 people such as () Anderson used type, and the continuous capsule of 327 guiding towards the central opening station thus.At opening station 327, lid paper tinsel 312a, 312b and substrate paper tinsel 314a, 314b (part of each band 300a, 300b) strippingly divide out around most advanced and sophisticated 309a, 309b.Substrate paper tinsel 314a, the 314b of the sky that produces coils in respective substrates coiling chamber 315a, 315b.Rotatable substrate winding main shaft 313a, 313b schedule the end anchor of each respective substrates paper tinsel 314a, 314b among its chamber 315a, the 315b.The progressive rotation of each respective substrates winding main shaft 313a, 313b causes " discarding " substrate paper tinsel 314a, 314b to be wound into tight volume around it.Generally speaking, the rotation of each substrate main shaft 313a, 313b is connected to the rotation of corresponding divided wheel 360a, 360b.
With the lid paper tinsel 312a, the 312b that cross through corresponding most advanced and sophisticated 309a, 309b presents and around corresponding lid reel 317a, 317b coiling, lid reel 317a, 317b also rotate with the lid of coiling on it paper tinsel 312a, 312b.Each lid reel 317a, 317b comprise central hub, central principal axis (not shown), lid paper tinsel 312a, 312b are attached on the central hub and around central hub and twine, and propeller boss can rotate and at central principal axis torsion spring (can not see) is installed around central principal axis.This specifically introduces in WO-A-2006/018261 (Glaxo Group Limited), the embodiment that in this application, introduces referring to Fig. 1 to Fig. 4 especially, this international application and be combined in herein by reference from the American National stage patent application that this application is derived.The function of torsion spring is to guarantee that lid reel 317a, 317b by it provide approximately constant driving tension force to each band 300a, 300b on the process of the whole length of each band.Especially, each torsion spring is wound into the variation of the driving tension force that compensation is associated with effective coiling diameter increase of each lid reel 317a, 317b when covering on the reel for little by little becoming at lid paper tinsel 312a, 312b with mistake.Therefore, can keep at whole band length the even calibration of each band 300a, 300b.
In use, shown in Fig. 3 a to 3c and Fig. 4 a to Fig. 4 c, the movement of (shown in Fig. 3 c and 4c) comes to drive ground rotary index wheel 360a, 360b and lid reel 317a, 317b advance each bubble- cap band 300a, 300b to the 3rd position from the second position (shown in Fig. 3 b and Fig. 4 b) by lid 300, thus make so that the capsule of its front portion is stripped allotter be ready to for.In order to approach the inclusions in the capsule of opening, then the patient sucks by interface 332.This causes negative pressure to be delivered to capsule in the front of opening of each band 300a, the 300b at opening station 327 by manifold 450.And therefore this each interior drug powder that has caused being contained in the capsule of opening also arrives the patient as inhalation group composite medicine dosage by common manifold 450 to interface 332 extractions simultaneously.This will more specifically introduce referring to Fig. 9 to Figure 13 hereinafter.
Now again referring to Fig. 5, can see that gear mechanism 340 comprises the ratchet gear 342 that is installed on the drive shaft 331.Ratchet gear 342 (similar other gear) is the wheel form with relative inner face 341 and outside 343 (with respect to the outside of allotter) and the outer circumferential surperficial 345a between them.Outside 343 be recessed into to limit the interior peripheral surface 345b that is in relativeness with outer circumferential surperficial 345a.As shown in the figure, outer circumferential surperficial 345a and interior peripheral surface 345b are provided with stepped profile and are used for producing the ratchet-type interaction with ratchet 346 to obtain corresponding outer ratchet part 344a and handle ratchet wheel part 344b, and this interaction will more specifically be introduced referring to Fig. 6 a to Fig. 6 c.Ratchet part 344a, 344b are the isolated hook tooths of equal angles; Have 5 teeth at each peripheral surface 345a, 345b in this embodiment.The outside tooth 344a on the peripheral surface 345a (" external tooth 344a ") and the skew of the tooth 344b (" internal tooth 344b ") on interior peripheral surface 345b.In other words, any one in the middle of the internal tooth 344b all is not positioned at the radius of identical with the external tooth 344a rotation axis apart from gear 342.
As from Fig. 6 a as seen, interior peripheral surface 345b comprises and connects each contiguous internal tooth to the surperficial sections 349 of 344b.Each surperficial sections 349 is comprised of the first section 349a, 349b, its opposed end from sections 349 extends internally, the first section 349a extends to Second Region section 349b to interior from an internal tooth 344b, and the second section 349b extends to introversive the first section 349a from next contiguous internal tooth 344b.The radius of curvature of the first section 349a is greater than the second section 349b, and the second section 349b forms the slope section with respect to the first section 349a thus.
Referring to Fig. 5, should be appreciated that the main shaft (not shown) of substrate winding main shaft 313a, 313b and lid reel 317a, 317b is connected respectively to substrate coiling gear 362a, 362b and lid coiling gear 361a, 361b. Divided wheel 360a, 360b also are provided with gear.The inner face 341 of ratchet gear 342 is provided with and transmits gear teeth 347 and be used for first gear with (i) divided wheel 360a, and (ii) driving of the first idle pulley 364 interact (engagement).The gear engagement of in the gear of the first divided wheel 360a and the lid reel gear 361 first and the second divided wheel 361b, and the gear of divided wheel 361b and the second lid coiling gear 361 mesh.Among the first idle pulley 364 and the substrate winding main shaft gear 362b first and 365 engagements of the second idle pulley, and the second idle pulley 365 and the second substrate winding main shaft gear 362a engagement.This gear train is arranged on interface lid 330 and provides the calibration of pharmaceutical carrier 300a, 300b and the upper volume of substrate sheet 310a and cover plate 312a during to its 3rd position movement from its second position.
The more specifically introduction that is used for the suitable counter mechanism of allotter provides at WO-A-2005/079727 (Glaxo Group Limited), this application and be attached to herein by reference from the American National stage patent application case that this application is derived.Substrate winding main shaft 313b can be used for driving this counter mechanism by engaging with its driving wheel/speed increasing gear.
To shown in Figure 7, ratchet 346 comprises central hub 346a such as Fig. 5, from the dangle elastic leg 346b of the isolated circumferential orientation of a plurality of equal angles of the periphery of this central hub 346a.Ratchet propeller boss 346a also comprises boss 346c, it is assemblied in shown in Fig. 4 a and is used to form interface lid 330 in the installation aperture 336 of interface lid arm 334 and is connected the rotary moving that the rotary moving of interface lid 330 in its primary importance to the three positions thus causes the ratchet 346 in ratchet gear 342 with direct driving between the ratchet 346, as will be hereinafter more specifically introducing subsequently.In this specific embodiment, ratchet lower limb 346b dangles from ratchet propeller boss 346a.In other words, the number of the internal tooth 344b of the number coupling ratchet gear 342 of selection ratchet lower limb 346b.
Can understand better the interaction of ratchet gear 342 and ratchet 346 referring to Fig. 6 a to Fig. 6 c, its show when in the consecutive steps corresponding with the consecutive steps of Fig. 3 a to Fig. 3 c, be ready to for the time the second pill dispenser the movement of parts of gear mechanism 340.
In the resting position (that is, interface lid 330 is closed) of Fig. 6 a, ratchet 346 is placed in the ratchet gear 342 angularly so that the internal tooth 344b of ratchet gear 342 is spaced apart at the free end of circumferential and ratchet lower limb 346b.In the second position (that is, interface lid 300 partially opens) of Fig. 6 b, ratchet 346 engages internal tooth 344b around rotation so that ratchet lower limb 346b slides at the neighbouring surface sections 349 of interior peripheral surface 345b in ratchet gear 342.Therefore should be appreciated that in this second position that ratchet gear 342 is ready for mobile but not yet mobile, and therefore general gear mechanism 340 and distributor gear 350a, 350b are not pushed into.In the 3rd position of Fig. 6 c (namely, interface lid 330 is opened fully), ratchet 346 rotate (72 ° as shown in the figure) with ratchet gear 342 by engaging between ratchet lower limb 346b and the internal tooth 344b thus advance total gear mechanism 340 and distributor gear 350a, 350b so that calibration and advance each pharmaceutical carrier 300a, 330b with the capsule of opening each carrier and therefore make the drug powder that is contained in each capsule of opening can be used for being sucked simultaneously by interface 332 by the patient at manifold 450 places at opening station 327.
Referring to Fig. 7, allotter comprises that also inner holding plate 381 is used for covering gear mechanism 340.Holding plate 381 is provided with segmental support 383, and it is positioned on ratchet gear 342 and the ratchet 346.One end of frame 383 is constructed to jerk-finger 384, wherein is provided with breach 385.Ratchet 346 comprises protruding 346d, and projection 346d engages breach when ratchet (with therefore interface lid 330) is in its first resting position of Fig. 6 a, as shown in Figure 7.Engaging between this ratchet projection 346d and the holding plate breach 385 played " interface is closed " or the resting position that are used for interface lid 330 is positioned Fig. 3 a, Fig. 4 a, Fig. 6 a and Fig. 7 of pallet.
Holding plate 381 comprises that also fixing elastic pawl lower limb 387 interacts to form " anti-returning " part of ratchet gear 346 with the external tooth 344a with ratchet gear 346.When interface lid 330 is opened, for ratchet lower limb 346a with make ratchet 346 and then ratchet gear 342 rotations after internal tooth 344 engages, ratchet lower limb 387 does not hinder ratchet gear 342 rotary movings, because ratchet lower limb 387 straddles on external tooth 344a, this is owing to their orientation and the elasticity of ratchet lower limb 387.Yet, when interface lid 330 turns back to its closed position, successively ratchet 346 is rotated to its resting position, engage by one among ratchet lower limb 387 and the external tooth 344a and keep ratchet gear 342 to prevent from returning rotation.Therefore, the counter-rotating of ratchet 346 is not delivered to gear mechanism 340 when down interface lid 330.Therefore, each interface lid 350 opens and closes fully, and 342 of ratchet gears increase in a direction of rotation.
Cover the position (a) (Fig. 6 is a) time, and elastic leg 346b slides back to be used for next time opening of interface lid 330 in the different spaced apart preparations in internal tooth 344b back at interior peripheral surface 345b so that the rotation of the ratchet 346 in the ratchet gear 342 turns back to its resting position for Fig. 3 when interface lid 330 turns back to its first.
In Fig. 6 a, illustrated divided wheel 360a gear teeth in an enlarged drawing, it shows its profile.Cogged gear teeth in gear mechanism is equipped with this profile.
Now hereinafter the manifold 450 of the second pill dispenser is launched to introduce more specifically referring to Fig. 9 to Figure 13.
Fig. 9 shows the second pill dispenser of the interface 332 of having removed it and the first case cover part 420a and the second case cover part 420b that shell 320 comprises cooperation.Manifold 450 is contained among the first case cover part 420a so that hold the antelabium of the entrance 453 that defines manifold chimney road 452 in the inwall 472 of the first closure shell part 420a, and the inwall 472 of the first case cover part 420a defines air intake grid 470.Manifold 450 also is housed inside among the second case cover part 420b so that the protrusion foot 455 of manifold 450 is installed in the manifold receptive cavity (not shown).
Shown in Fig. 3 a to Fig. 3 c, air intake grid 470 in the first case cover part 420a is in first or (Fig. 3 is covered by interface lid 330 a) time in the closed position when interface lid 330, second or semi-open position (the during Fig. 3 b) part that is in it when interface lid 330 is not covered, and manifests fully when middle when interface lid 330 is in its 3rd or open position (Fig. 3 c).
In use, the response patient is air-breathing interface 332, and air intake grid 470 allows air to enter in the manifold 450 from dispenser exterior via the chimney road entrance 453 to chimney road 452.Especially, air intake grid 470 provides the unique air amount inlet point in the manifold 450 of air amount from the second pill dispenser outside to it.
It can also be seen that referring to Figure 10 and Figure 11, manifold 450 has specific inner structure, wherein chimney road 452 is positioned at the top of chamber 460 and partly shares a common wall 459 with it, and this common wall 459 forms the diapire (with respect to shown orientation) in chimney roads 452 and the roof (with respect to shown orientation) of chamber 460.
Chimney road 452 has chimney road entrance 453 and the outlet of a pair of chimney road 454a, 454b.In use, chimney road 452 inwardly guides air flow (it receives by air intake grid 470 fully) from chimney road entrance 453 to this chimney road outlet to 454a, 454b when the patient sucks.Chamber 460 has a pair of chamber entrance 462a, 462b (only to see one) and chamber outlet 464.The outlet of chimney road is all limited by a pair of circular hole 462a, 462b 454a, 454b and chamber entrance, in this specific embodiment, and the about 3mm of diameter, and each hole is provided with corresponding cross 451,461.A pairing among each chimney road outlet 454a, 454b and chamber entrance 462a, the 462b, this pairing is by being close to mutually positioning formation with them.Interface 332 be provided to chamber outlet 464 and via buckle mounting parts 465 buckle be installed to it above.
Specifically introduce as mentioned, when interface lid 330 is opened to its 3rd position fully, actuated gear and distributor gear so that advance the single capsule of each bubble- cap band 300a, 300b and each band of strip off.The blister (not shown) of each strip off of each band 300a, 330b is arranged in contiguous chimney road outlet to 454a, 454b and the chamber entrance corresponding place to 462a, 462b.When the patient when interface 332 sucks, air-flow is only by 452 interior air intake grids 470 enter in the manifold 450 from the outside of allotter to the chimney road.The first of this air-flow flow in the blister of opening of each band 300a, 300b via corresponding chimney road outlet 454a, 454b, thereby in air-flow, carry the drug powder that is contained in the capsule secretly, and from then on flow out in the chamber 460 from capsule via chamber entrance 462a, 462b.Then the air-flow that is entrained with drug powder flows out in patient's the respiratory tract from interface 332.
As shown in figure 12, for example, single D shape (bleed) hole 480 of bleeding is located on the wall 459, and wall 459 separates chimney road 450 and chamber 460.D shape aspirating hole 480 is positioned at contiguous chimney road outlet 454a, 454b and chamber entrance 462a, 462b place.In use, aspirating hole 480 second portion from chimney road 452 to cavity that be used for the 460 interior steering currents (" part of bleeding ") from is with the first of the drug powder that impacts devastatingly transportation and carry secretly the air-flow in the chamber 460 and so smash its any powder agglomates composition.
Figure 13 shows the second manifold 550, and it is the modification (with alternative manifold) of the manifold 450 of band " D hole " type aspirating hole 480.
Should be appreciated that the overall shape of this second manifold 550 and form responding in total shape of " D hole " manifold 550 and form so that these two can substitute each other.Yet the second manifold has aspirating hole 580a, the 580b of two elongated slot forms, and it is located on the wall 559, and wall 559 separates chimney road 552 and chamber (can not see).
More specifically, the second manifold 550 has inner structure, wherein chimney road 552 be positioned at chamber (can not see) top and partly with its common wall 559, this wall 559 forms the diapire (as shown in the figure) in chimney roads 552 and the roof of chamber (can not see).
Chimney road 552 has chimney road entrance 553 and two outlets of chimney road 554a, 554b.In use, chimney road 552 exports 454a, 454b and inwardly guides air flow (it all receives by air intake grid 470) from chimney road entrance 553 to the chimney road.Chamber has two chamber entrances (can not see) and chamber outlet 564.Outlet 554a, 554b are the same with the first manifold 450 with the chamber entrance in the chimney road.
Situation as the first manifold 450, chimney road outlet 554a, 554b and chamber entrance are located adjacent one another to form pairing, the blister of opening from each strippable bubble-cap band is placed so that when the patient is air-breathing against these paired outlets and entrance, air-flow all flows in the manifold chimney roads 552 via air intake grid 470, and wherein the capsule guiding of opening is passed from the capsule of opening drug powder is entrained in the chamber via paired chimney road outlet 554a, 554b and chamber entrance by the first of air-flow.
Aspirating hole 580a, the 580b of elongated slot form is located on the wall 559, and wall 559 separates chimney road 552 and chamber (can not see).Aspirating hole 580a, the 580b of elongated slot form is positioned at apart from the chimney road and exports 554a, 554b and chamber entrance at a distance.In use, the part of bleeding of steering current partly was entrained to the drug powder in the chamber and therefore smashes its any powder agglomates composition to impact devastatingly by the first air-flow in aspirating hole 580a, 580b were used for from chimney road 552 to chamber.
Manifold 450,550 can be entirely partly comprise or optionally entirely or partly coating reduce medicine and adhere to its top tendentious material.These materials can (for example) improve the surface tension on associated manifolds surface.Can adopt fluorinated polymer material.High density polyethylene (HDPE) (HDPE) and/or modification acetal material also are suitable.
Therefore visible the second pill dispenser provides the movement of interface lid 330 to actuate allotter and also activator batching counter in this embodiment.The second pill dispenser also provides lid 330 not cause actuating of allotter to the movement that partially opens position (primary importance) and (in this embodiment) do not cause actuating of dose counter yet.This allows the patient to clean interface 232 and reduces the careless or unexpected probability of using of allotter, when interface lid 230 is moved back and forth or played with to (for example) the patient.
Although about the allotter that comprises two pharmaceutical carrier 300a, 300b the second pill dispenser of Fig. 3 to Figure 13 has been launched introduction, but should be appreciated that same allotter can be used for single pharmaceutical carrier, wherein in the distributor gear is not worked to any pharmaceutical carrier.Perhaps, each pharmaceutical carrier can comprise identical drug powder (that is, identical active or active combination).
The most of member that it will be understood by a person skilled in the art that pill dispenser of the present invention can be made by plastic material, and for example, the molded plastic material member is usually by injection moulding.In the second pill dispenser of Fig. 3 to Figure 13, all members except torsion spring (it can be made by rustless steel) can be made by plastic material (for example, injection moulding).In this case, except following plastic member, all plastic members can be acetal (polyformaldehyde (POM)):
Case body 420a, 420b-acrylonitrile-butadiene-styrene copolymer (ABS)
Interface lid 330-ABS
Counter wheel (not shown)-ABS
Manifold 450,550-high density polyethylene (HDPE) (HDPE)
Enumerator window 324-Merlon (PC)
Interface 332-polypropylene (PP)
Pill dispenser of the present invention is fit to distribute pharmaceutical preparation, is particularly suitable for treating respiratory system disease such as asthma and chronic obstructive pulmonary disease (COPD), bronchitis and chest infection.
Therefore suitable medicine can be selected from for example analgesics, such as codeine, paramorphane, Ergotamine, fentanyl or morphine; Anginal preparations is such as diltiazem; Anti-allergic agent is such as cromoglycate (as sodium salt), ketotifen or nedocromil (as sodium salt); Anti-infective is such as cephalosporins, penicillins, streptomycin, sulfonamides, Tetracyclines and pentamidine; Antihistaminic is such as methapyrilene; Antiinflammatory, such as beclometasone (as dipropionate), fluticasone (as propionic ester), flunisolide, budesonide, rofleponide, mometasone (as furoate), ciclesonide, triamcinolone (as acetonide) or 6 α, 9 alpha-difluoro-11 betas-hydroxy-16 alpha--methyl-3-oxo-17 α-propionyloxy-androstane-Isosorbide-5-Nitrae-diene-17 β-thiocarboxylic acid S-(2-oxo-tetrahydrochysene-furan-3-yl) ester; Antitussive is such as narcotine; Bronchodilator is such as albuterol (as free alkali or sulfate), salmaterol (as xinafoate), ephedrine, epinephrine, fenoterol (as hydrobromate), formoterol (as fumarate), isoproterenol, orciprenaline, phenylephrine, phenylpropanolamine, pirbuterol (as acetate), reproterol (as hydrochlorate), rimiterol, terbutaline (as sulfate), neoisuprel, tulobuterol or 4-hydroxyl-7-[2-[2-[[3-(2-phenyl ethoxy) propyl group] sulfonyl] ethyl] amino] ethyl-2 (3H)-benzothiazolone; Adenosine 2a agonist, such as 2R, 3R, 4S, 5R)-2-[6-amino-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purine-9-yl]-5-(2-ethyl-2H-tetrazolium-5-yl)-tetrahydrochysene-furan-3,4-glycol (as maleate); α 4 integrin inhibitors are such as (2S)-3-[4 ({ [4-(amino carbonyl)-piperidino] carbonyl } oxygen base) phenyl]-2-[((2S)-and 4-methyl-2-{[2-(2-methylphenoxy) acetyl group] amino } valeryl) amino] propanoic acid (as free acid or potassium salt); Diuretic is such as amiloride; Cholilytic drug is such as ipratropium bromide (as bromide), tiotropium bromide, atropine or oxitropium bromide; Hormone is such as cortisone, hydrocortisone or prednisone; Xanthine is such as aminophylline, Oxtriphylline, theophylline-lysine or theophylline; Therapeutic protein and peptide class are such as insulin or glucagon; Vaccine, diagnosis and gene therapy.It will be appreciated by one of skill in the art that the medicine that can use salt (as alkali metal or amine salt or as acid-addition salts), ester (such as lower alkyl esters) or solvate (such as hydrate) form when suitable, to optimize the active and/or stable of described medicine.
The pharmaceutical preparation of preparation can be monotherapy (namely containing single active medicine of planting) goods, perhaps can be combination treatment (namely containing the various active medicine) goods.
The suitable drug of combination treatment goods or ingredient are selected from antiinflammatory (such as corticosteroid or NSAID), cholilytic drug usually (such as M 1, M 2, M 1/ M 2Or M 3Receptor antagonist), other β 2-adrenoceptor agonists, anti-infective (such as antibiotic or antiviral agent) and hydryllin.Comprise the combination that all are suitable.
Suitable antiinflammatory comprises corticosteroid and NSAID.Suitable corticosteroid is to have the oral of anti-inflammatory activity and suck corticosteroid and prodrug thereof.Example comprises methyl meticortelone, meticortelone, dexamethasone, fluticasone propionate, 6 α, 9 α-two fluoro-, 17 α-[(2-furyl carbonyl) oxygen base]-11 beta-hydroxy-16 Alpha-Methyls-3-oxo-androstane-1,4-diene-17 β-thiocarboxylic acid S-fluorine methyl ester, 6 α, 9 alpha-difluoro-11 betas-hydroxy-16 alpha--methyl-3-oxo-17 α-propionyloxy-androstane-1,4-diene-17 β-thiocarboxylic acid S-(2-oxo-oxolane-3S-yl) ester, beclomethasone ester (such as 17-propionic ester or 17,21-dipropionate), budesonide, flunisolide, mometasone ester (such as furoate), triamcinolone acetonide, rofleponide, ciclesonide, butixocort propionate, RPR-106541 and ST-126.Preferred corticosteroid comprises fluticasone propionate, 6 α, 9 alpha-difluoro-11 betas-hydroxy-16 alpha--methyl-17-alpha-[(4-methyl isophthalic acid, 3-thiazole-5-carbonyl) oxygen base]-3-oxo-androstane-1,4-diene-17 β-thiocarboxylic acid S-fluorine methyl ester and 6 α, 9 α-two fluoro-, 17 α-[(2-furyl carbonyl) oxygen base]-11 beta-hydroxy-16 Alpha-Methyls-3-oxo-androstane-1,4-diene-17 β-thiocarboxylic acid S-fluorine methyl ester, more preferably 6 α, 9 α-two fluoro-, 17 α-[(2-furyl carbonyl) oxygen base]-11 beta-hydroxy-16 Alpha-Methyls-3-oxo-androstane-Isosorbide-5-Nitrae-diene-17 β-thiocarboxylic acid S-fluorine methyl ester.
Suitable NSAID comprises sodium cromoglicate, sodium nedocromil, phosphodiesterase (PDE) inhibitor is (such as theophylline, PDE4 inhibitor or hybrid PDE 3/PDE4 inhibitor), leukotriene antagonist, the inhibitor that leukotriene is synthetic, the iNOS inhibitor, trypsinlike enzyme and elastatinal, β-2 integrin antagonists and adenosine receptor agonist or antagonist (such as adenosine 2a agonist), cytokine antagonist (such as chemokine antagonists) or cytokine synthetic inhibitor.Other suitable β 2-adrenoceptor agonists comprises salmaterol (as xinafoate), albuterol (as sulfate or free alkali), formoterol (as fumarate), fenoterol or terbutaline and salt thereof.
Suitable phosphodiesterase 4 (PDE4) inhibitor comprises the known PDE4 of inhibition enzyme or finds to serve as the chemical compound of PDE4 inhibitor that described chemical compound is the PDE4 inhibitor, is not the chemical compound that suppresses PDE4 and other members of PDE family.Usually preferably use IC 50Ratio is about PDE4 inhibitor more than 0.1, and described ratio is the IC of the PDE4 catalysis form of being combined with the rolipram high-affinity 50Divided by with the IC of rolipram low-affinity combining form 50For purpose of the present disclosure, to be called " low-affinity " binding site (LPDE4) with the cAMP catalytic site that R and S rolipram low-affinity are combined, other form of this catalytic site of being combined with the rolipram high-affinity is called " high-affinity " binding site (HPDE4).Term " HPDE4 " and the term " hPDE4 " that is used for namer PDE4 should not obscured.
Be used for determining IC 50The method of ratio is at United States Patent (USP) 5,998, lists in 428, and it is attached to herein as listing fully at this paper by reference.Also consult PCT application WO 00/51599 about the another kind description of described mensuration.
Suitable PDE4 inhibitor comprises those chemical compounds with useful treatment rate, the chemical compound that namely preferably suppresses the cAMP catalytic activity of wherein enzyme employing and the combining form of rolipram low-affinity, thereby the obvious relevant side effect of minimizing and inhibition and the combining form of rolipram low-affinity.The mode of another kind of explanation is that preferred compound will have about IC more than 0.1 50Ratio, described ratio are the IC of the PDE4 catalysis form of being combined with the rolipram high-affinity 50Divided by with the IC of rolipram low-affinity combining form 50
More accurate standard is that wherein the PDE4 inhibitor has about IC more than 0.1 50Ratio; Described ratio is and 1nM[ 3H] the R-rolipram is in conjunction with the IC of the PDE4 form of being combined with the rolipram high-affinity of competition 50Value with 1 μ M[ 3H]-cAMP makes the IC of the inhibition PDE4 catalytic activity of the form that substrate is combined with the rolipram low-affinity 50The ratio of value.
Optimal is the IC that has greater than 0.5 50The PDE4 inhibitor of ratio particularly has those chemical compounds greater than 1.0 ratios.Preferred compound is cis 4-cyano group-4-(3-cyclopentyloxy-4-methoxyphenyl) cyclohexane extraction-1-carboxylic acid, 2-carboxymethoxyl-4-cyano group-4-(3-cyclo propyl methoxy-4-difluoro-methoxy phenyl) hexamethylene-1-ketone and cis-[4-cyano group-4-(3-cyclo propyl methoxy-4-difluoro-methoxy phenyl) hexamethylene-1-alcohol]; These are preferred be combined with the low-affinity binding site and have 0.1 an above IC 50The examples of compounds of ratio.
Other suitable medical compounds comprises: be disclosed in United States Patent (USP) 5,552,438 cis-4-cyano group-4-[3-(cyclopentyloxy)-4-methoxyphenyl] cyclohexane extraction-1-carboxylic acid (being also referred to as cilomalast) and salt, ester, prodrug or physical form; The AWD-12-281 of elbion (Hofgen, N. etc., 15th EFMC Int Symp Med Chem (Sept 6-10, Edinburgh) 1998, Abst is P.98; CAS reference number 247584020-9); The 9-benzyladenine derivant (INSERM) that is called NCS-613; The D-4418 of Chiroscience and Schering-Plough; The benzodiazepine that is called CI-1018 that belongs to Pfizer
Figure 2006800351868_5
PDE4 inhibitor (PD-168787); Be disclosed in the benzo dioxane pentadiene of WO99/16766 by KyowaHakko; The K-34 of Kyowa Hakko; The V-11294A of Napp (Landells, L.J. etc., Eur Resp J[Annu Cong EurResp Soc (Sept 19-23, Geneva) 1998] 1998,12 (Suppl.28): Abst P2393); The roflumilast of Byk-Gulden (CAS reference number 162401-32-3) and pthalazinone (WO99/47505, it discloses incorporated herein by reference); Pumafentrine, (-)-p-[(4aR *, 10bS *)-9-ethyoxyl-1,2,3,4,4a, 10b-six hydrogen-8-methoxyl group-2-methyl benzo [c] [1,6] naphthyridines-6-yl]-N, N-diisopropyl Benzoylamide is hybrid PDE 3/PDE4 inhibitor, by the Byk-Gulden preparation that now is called Altana and open; Arofylline by the Almirall-Prodesfarma exploitation; The VM554/UM565 of Vernalis; Perhaps T-440 (Tanabe Seiyaku; Fuji, 162) and T2585 K. etc., J Pharmacol Exp Ther, 1998,284 (1):.
Suitable cholilytic drug is as those chemical compounds, particularly M1 of muscarinic receptor antagonist and those chemical compounds of M2 receptor antagonist.Exemplary chemical compound comprises the alkaloid of Semen daturae plant, for example atropine, scopolamine, melyltropeine, hyoscyamine; Usually with these chemical compounds as the salt administration, be tertiary amine.
Ipratropium bromide (as bromide), oxitropium bromide (as bromide) and tiotropium bromide (as bromide) that specially suitable cholilytic drug comprises commodity Atem by name are (CAS-13940-48-1).The cholilytic drug of no less important is: Methantheline (CAS-53-46-3), propantheline bromide (CAS-50-34-9), bromomethyl Anisotropine or Valpin 50 (CAS-80-50-2), clidinium bromide (Quarzan, CAS-3485-62-9), copyrrolate (Robinul), isopropamide iodide (CAS-71-81-8), mepenzolate bromide (United States Patent (USP) 2,918,408), tridihexethyl chloride (Pathilone, CAS-4310-35-4) and hexocyclium metilsulfate (Tral, CAS-115-63-9).The chemical compound that also has cyclopentolate hydrochloride (CAS-5870-29-1), holder bicalutamide (CAS-1508-75-4), benzhexol hydrochloride (CAS-144-11-6), pirenzepine (CAS-29868-97-1), telenzepine (CAS-80880-90-9), AF-DX 116 or Methoctramine and be disclosed in WO01/04118.
Suitable hydryllin (is also referred to as H 1-receptor antagonist) comprises any or multiple known H of inhibition 1-receptor is also used multiple antagonist in human body safely.All be and histamine H 1The reversibility of-acceptor interaction, competitive inhibitor.Example comprises ethanolamine, ethylenediamine and alkylamine.In addition, other first generation hydryllin comprises the hydryllin that can have piperazine and phenothiazinyl eigen.Second filial generation antagonist without sedation has similar structure-activity relation, because they keep core ethylidene (alkylamine) or have the tertiary amine groups of simulation piperazine or piperidines.Exemplary antagonist is as follows:
Ethanolamines: carbinoxamine maleate, clemastine fumarate, hydrochloric acid two phenylhydroxyamines and dimenhydrinate.
Ethylenediamines: mepyramine maleate, tripelennamine hydrochloride and citric acid tripelennamine.
Alkyl amine: chlorphenamine and salt thereof such as maleate and acrivastine.
Piperazines: hydroxyzine hydrochloride, pounce on sour hydroxyzine, cyclizine hydrochloride, cyclizine lactate, meclozine hydrochloride and cetirizine hydrochloride.
Piperidines: astemizole, hydrochloric acid levocabastine, loratadine or its decarboxylation ethyoxyl analog, and terfenadine and fexofenadine hydrochloride or another kind of pharmaceutically acceptable salt.
A-5610 is to unite with the PDE4 inhibitor the another kind of H of use 1Receptor antagonist.
Particularly suitable hydryllin comprises methapyrilene and loratadine.
Aspect compound artifact, the experiment basis of known method is depended in the compound formulation compatibility usually, can be dependent on the pill dispenser type of action of selection.
The ingredient of compound artifact suitably is selected from antiinflammatory (such as corticosteroid or NSAID), cholilytic drug (such as M 1, M 2, M 1/ M 2Or M 3Receptor antagonist), other β 2-adrenoceptor agonists, anti-infective (such as antibiotic or antiviral agent) and hydryllin.Comprise the combination that all are suitable.
Compound formulation compatibility composition suitably comprises β 2-adrenoceptor agonists and corticosteroid; Compound formulation incompatibility composition comprises PDE-4 inhibitor, cholilytic drug or its mixture.β 2-adrenoceptor agonists can be for example albuterol (as free alkali or sulfate) or salmaterol (as xinafoate) or formoterol (as fumarate).Corticosteroid can be for example beclomethasone ester (such as dipropionate) or fluticasone ester (such as propionic ester) or budesonide.
In an example, compound formulation compatibility composition comprises fluticasone propionate and salmaterol or its salt (particularly xinafoate), and compound formulation incompatibility composition comprises PDE-4 inhibitor, cholilytic drug (such as ipratropium bromide or tiotropium bromide) or its mixture.
In another example, compound formulation compatibility composition comprises budesonide and formoterol (as fumarate), and compound formulation incompatibility composition comprises PDE-4 inhibitor, cholilytic drug (such as ipratropium bromide or tiotropium bromide) or its mixture.
Usually, be fit to be delivered to aerodynamic diameter that the powdered drug granule of bronchus or alveolar region has less than 10 microns, preferred 1-6 micron.If need to be delivered to respiratory tract other parts such as nasal cavity, mouth or throat, can use other big or small granule.Although medicine can be sent as pure medicine, more suitable is preferably medicine to be sent with the excipient (carrier) that is fit to suck.Suitable excipient comprises organic excipients such as polysaccharide (being starch, cellulose etc.), lactose, glucose, mannitol, aminoacid and maltodextrin, and inorganic excipients such as calcium carbonate or sodium chloride.Preferred excipient is lactose.
The granule of powdered drug and/or excipient can prepare with routine techniques, as by micronization, grind or sieve.In addition, can design concrete density, magnitude range or the feature of medicine and/or excipient powders.Granule can comprise other composition that activating agent, surfactant, one-tenth wall material or those skilled in the art see fit.
Can excipient be comprised with medicine by well-known method, as passing through mixing, co-precipitation etc.Usually the mixture of preparation excipient and medicine is separated into dosage with accurate measurement with mixture.For example, correct mixture comprises 13000 milligrams of lactose with 50 milligrams of medicament mixed, and the ratio that obtains excipient and medicine is 260: 1.Can use excipient and medicine ratio is 100: 1-1: 1 dosage mixture.But when the ratio of excipient and medicine hanged down very much, it is more diversified that the drug dose reproducibility can become.
Pill dispenser of the present invention is fit to distribute the medicine that is used for the treatment of respiratory system disease on the one hand, and described disease such as lung and bronchial disease comprise asthma and chronic obstructive pulmonary disease (COPD).On the other hand, pill dispenser of the present invention is fit to a minute medicine, and described medicine is used for the treatment of needs by the disease of the systemic circulation treatment of medicine, such as migraine, diabetes, alleviating pain such as the suction morphine.
Therefore, this paper provides the purposes of pill dispenser treatment respiratory system disease such as asthma and COPD.Perhaps, the invention provides the method for the treatment of respiratory system disease such as asthma and COPD, described method comprises the pharmaceutical preparation administration described herein by effective dose in the pill dispenser that sucks this paper.
Certainly, realize the amount of any concrete medical compounds that the treatment effect needs or its pharmaceutically acceptable salt, solvate or physiologic function derivant will be according to particular compound, route of administration, changed by treatment target and subject concrete disease or disease.For example, the inhalation dosage of the medicine for the treatment of this paper respiratory system disease can be 0.0005mg-10mg, preferred 0.005mg-0.5mg.Adult's dosage range is generally 0.0005mg-100mg every day, preferred every day 0.01mg-1mg.
It is only presented for purposes of illustration to understand the disclosure, and the present invention can comprise its modification of carrying out, change and improvement.
The All Files of this paper reference all is attached to herein by reference.

Claims (34)

1. a pill dispenser is used for using with at least one pharmaceutical carrier of the multiple different pharmaceutical part of carrying, and described pill dispenser comprises:
(a) distributor gear, it can actuate the described different pharmaceutical part of being carried by described at least one pharmaceutical carrier for distributing;
(b) interface; And
(c) be used for the lid of described interface, described lid is installed on the described allotter movably for the primary importance that is covered from described interface, the second position that is not covered to described interface section, the 3rd position continuous moving that is not covered to described interface;
Wherein, described lid is suitable for connecting with described distributor gear so that movement rather than the described primary importance of described lid from the described second position to described the 3rd position causes actuating of described distributor gear to the movement of the described second position.
2. pill dispenser according to claim 1 is characterized in that, comprises a plurality of described pharmaceutical carriers, and each pharmaceutical carrier carries a plurality of different drug dose parts.
3. pill dispenser according to claim 1 is characterized in that, described at least one pharmaceutical carrier is the pharmaceutical carrier of elongated form.
4. pill dispenser according to claim 1 is characterized in that, described distributor gear comprises:
I) receiving station is used for receiving each pharmaceutical carrier;
Ii) releasing device is used for discharging the different pharmaceutical part from each pharmaceutical carrier when receiving described pharmaceutical carrier by described receiving station;
Iii) outlet is used for partly being communicated with described interface and with the described different pharmaceutical of each pharmaceutical carrier that can be discharged by described releasing device; And
Iv) indexer is used for the individually described different pharmaceutical part of each pharmaceutical carrier of calibration.
5. according to each described pill dispenser of aforementioned claim, it is characterized in that described lid directly connects with described distributor gear.
6. pill dispenser according to claim 1 is characterized in that, described lid mechanically connects with described distributor gear.
7. pill dispenser according to claim 1 is characterized in that, described distributor gear in the shell of described pill dispenser and described lid be connected movably with the shell of described pill dispenser.
8. pill dispenser according to claim 7, the shell of wherein said pill dispenser limits the entrance of interface, it is arranged so that this entrance is covered by it when described interface lid is in primary importance, part is not covered by it when described interface lid is in the second position, manifests fully when described interface lid is in the 3rd position.
9. pill dispenser according to claim 1 is characterized in that, described lid is provided on the rotate path mobile.
10. pill dispenser according to claim 1, it is characterized in that, the ratchet of described lid and described distributor gear interacts, and the transmission gear selection of the ratchet of described distributor gear and described distributor gear ground interacts to drive described distributor gear.
11. pill dispenser according to claim 10, it is characterized in that it is suitable for described ratchet being disengaged with described travelling gear and described ratchet being engaged with described travelling gear at described lid.
12. pill dispenser according to claim 10 is characterized in that, described distributor gear is provided with and anti-return part described travelling gear returns movement when mobile to prevent from returning from described the 3rd position to described primary importance at described lid.
13. pill dispenser according to claim 4, it is characterized in that, be used for using with the pharmaceutical carrier of one or more blister strips band forms, each pharmaceutical carrier has a plurality of different capsules and is used for comprising the drug dose part, wherein said capsule is spaced apart and be defined between described two peelable along two peelable length fixed to one another, and wherein said releasing device comprises detacher, described detacher is positioned to be bonded on substrate sheet and the cover plate of the capsule that receives in the described receiving station, is used for the described substrate sheet of strip off and cover plate to open described capsule.
14. pill dispenser according to claim 2 is characterized in that, the different pharmaceutical part of described at least one pharmaceutical carrier carrying powder type.
15. pill dispenser according to claim 1 is characterized in that, comprises the pharmaceutical carrier of the different pharmaceutical part of single carrying powder type, wherein each drug moiety comprises that bronchodilator and antibiotic medicine are as its active pharmaceutical ingredient.
16. pill dispenser according to claim 14, it is characterized in that, comprise two pharmaceutical carriers, wherein each drug dose of the first pharmaceutical carrier comprises that partly bronchodilator comprises partly that as each drug dose of active pharmaceutical ingredient and the second pharmaceutical carrier the antibiotic medicine is as active pharmaceutical ingredient.
17. pill dispenser according to claim 15 is characterized in that, described bronchodilator is that beta-2-agonists and described antibiotic medicine are corticosteroid.
18. pill dispenser according to claim 1 is characterized in that, described lid be adapted to be that the movement of described lid from the described second position to described the 3rd position causes actuating of described distributor gear connecting of described distributor gear.
19. pill dispenser according to claim 18, it is characterized in that, described distributor gear comprises first and second portion and the interface between described first and described second portion, described lid be connected in the described first and described first along with lid moves, described second portion can be driven so that described at least one pharmaceutical carrier executable operations is distributed described different pharmaceutical part by described first, and described interface is suitable for making described first to be merely able to drive described second portion at described lid when the described second position moves to described the 3rd position.
20. pill dispenser according to claim 19 is characterized in that, described interface is formed by ratchet device.
21. pill dispenser according to claim 20 is characterized in that, described ratchet device comprises ratchet and travelling gear.
22. pill dispenser according to claim 10 is characterized in that, described ratchet and travelling gear are respectively equipped with at least one first ratchet part and the second ratchet part to provide described ratchet to engage with the unidirectional drive of travelling gear.
23. pill dispenser according to claim 20, it is characterized in that, described ratchet device has the first member and second component, and described the first member and second component are respectively equipped with at least one first ratchet part and the second ratchet part to provide described the first member to engage with unidirectional drive between the described second component.
24. pill dispenser according to claim 22, it is characterized in that, described at least one first ratchet part and the second ratchet part be constructed and arranged to after the described lid of described the 3rd position movement except when lid they are disengaged during from the described second position to described the 3rd location positioning.
25. pill dispenser according to claim 10 is characterized in that, described lid is connected on the described ratchet.
26. pill dispenser according to claim 23 is characterized in that, described lid is connected on described the first member.
27. pill dispenser according to claim 2, it is characterized in that, described allotter is suction apparatus, the described drug dose of each carrier partly is that powder type and described allotter are suitable for allowing user air-breathing so that user sucks described drug dose part simultaneously at described interface, and described drug dose part is being moved to described the 3rd position and distributed from described pharmaceutical carrier by described distributor gear when actuating described distributor gear from the described second position by described lid.
28. pill dispenser according to claim 22 wherein has the first ratchet part and the second ratchet part of same quantity.
29. pill dispenser according to claim 22, wherein said at least one second ratchet part comprises the peripheral surface with stepped profile.
30. pill dispenser according to claim 29, wherein said peripheral surface are the interior peripheral surface of the recess that forms in the travelling gear.
31. pill dispenser according to claim 30, wherein said stepped profile provides a plurality of teeth, with at least one the surperficial sections that is connected contiguous described tooth, wherein said at least one surperficial sections comprises the first section and the second section, the radius of curvature of the first section is greater than the second section, and the second section forms the slope section with respect to the first section thus.
32. pill dispenser according to claim 22, wherein said ratchet comprises the ratchet propeller boss, and described at least one first ratchet part is at least one ratchet lower limb, and the ratchet lower limb dangles from the ratchet propeller boss, has the free end in propeller boss distally.
33. pill dispenser according to claim 32, wherein said at least one first ratchet part and at least one the second ratchet part be arranged so that primary importance at lid, the free end of described at least one ratchet lower limb and the tooth of travelling gear are circumferentially spaced apart, described lid makes described free end and indented joint to the movement of the second position, thereby make not rotary transmission gear of the movement of described lid from primary importance to the second position, but described lid rotates ratchet and travelling gear together to the movement of the 3rd position.
34. pill dispenser according to claim 33, wherein said lid rotates ratchet and travelling gear together to the gear mechanism that moves through of the 3rd position, with described at least one pharmaceutical carrier of calibration, and distribute at least one the different drug moiety that is carried by described at least one pharmaceutical carrier.
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